Postburn suppression of murine lymphocyte and neutrophil functions is not reversed by prostaglandin blockade.
Certain arachidonic acid metabolites, including prostaglandins (PGs) E1 and E2, have been shown to exert marked immunosuppressive effects on T-cell and macrophage functions. Cyclooxygenase blockade with indomethacin or ibuprofen may ameloriate these effects. In the current study we measured lymphocyte proliferation by thymidine incorporation, the presence of T-cell activation antigens with monoclonal antibodies and two-color flow cytometry, and neutrophil (PMN) oxidative burst using a fluorescent marker, in control mice and in burned mice treated with indomethacin for 10 days after injury. One-half of the cell cultures were treated with indomethacin in vitro to ensure its continued presence during stimulation. Separate groups of mice were fed a fish oil-based diet which leads to the production of PGE3 rather than PGE2, versus standard mouse chow, a soy-bean oil-based diet which leads to PGE2 production. Lymphocyte proliferation, expression of T-cell activation antigens, and PMN oxidative burst remained depressed in burned mice treated with indomethacin in vivo (plus in vitro) and in those which received the fish oil-based diet, compared to control. Blockade of PG synthesis after murine burn injury by cyclooxygenase inhibition or alterations in the diet failed to restore T-lymphocyte activation or proliferation or to improve PMN oxidative burst. These data suggest that PGE2 alone does not explain the immunosuppression noted after burn injury.
Gadd
M A
MA
Department of Surgery, University of California San Diego Medical Center 92103.
Hansbrough
J F
JF
D000818:Animals; D002056:Burns / Q000378:metabolism / Q000503:physiopathology*; D002455:Cell Division / Q000187:drug effects; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology; D005260:Female; D005395:Fish Oils / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000502:physiology*; D051379:Mice; D008815:Mice, Inbred Strains; D009504:Neutrophils / Q000378:metabolism / Q000502:physiology*; D010084:Oxidation-Reduction / Q000187:drug effects; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D012016:Reference Values; D013601:T-Lymphocytes
D004042:Dietary Fats, Unsaturated; D005395:Fish Oils; D011448:Prostaglandin Antagonists; D015232:Dinoprostone; D007213:Indomethacin